Thoughts on group A streptococci
Authors: Dingle Yu, Yunmei Liang, Qinghua Lu, Yuejie Zheng, George Fu Gao, Yonghong Yang
Journal: The Lancet Microbe (2023)

The increase in scarlet fever and invasive infections of group A Streptococcus (iGAS) in the UK and other European countries in 2022 has caused worldwide concern.1Ledford H Why is strep A surging—and how worried are scientists?.Nature. 2022; 612: 603Crossref PubMed Scopus (4) Google Scholar, 2Pigeolet M Haumont E Rubinsztajn R Pannier S Gaumé M Increase in paediatric group A streptococcal infections.Lancet Infect Dis. 2023; 23: 282Summary Full Text Full Text PDF PubMed Google Scholar, 3Venkatesan P Rise in group A streptococcal infections in England.Lancet Resp Med. 2023; 11: e16Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 4The Lancet MicrobeStrep A treatment, working for now.Lancet Microbe. 2023; 4: 1Summary Full Text Full Text PDF Scopus (1) Google Scholar In this Comment, we share our views on the unresolved factors pertaining to GAS infections. GAS, also known as Streptococcus pyogenes, is a highly important pathogen, ranking among the ten main causes of death from infectious diseases worldwide, with more than 517 000 deaths being attributed to the bacteria annually.5Carapetis JR Steer AC Mulholland EK Weber M The global burden of group A streptococcal diseases.Lancet Infect Dis. 2005; 5: 685-694Summary Full Text Full Text PDF PubMed Scopus (2012) Google Scholar GAS can cause a broad spectrum of clinical infectious diseases, ranging from mild diseases (eg, pharyngitis and impetigo) to life-threatening invasive infections, such as sepsis and streptococcal toxic shock syndrome (STSS). Moreover, GAS can also cause post-streptococcal complications, such as rheumatic fever, rheumatic heart disease, and acute post-streptococcal glomerulonephritis (APSGN). The diseases caused by GAS are therefore relevant to multiple medical disciplines, including paediatrics, infectious diseases, respiratory medicine, intensive care, rheumatology, cardiology, nephrology, dermatology, and even surgery. Rarely is a bacterium associated with such a broad range of specialties. After GAS infections, some people can develop rheumatic fever, and others APSGN. The mechanism of differentiation between post-streptococcal complications is unclear. Professor Singh Chhatwal's team (Helmholtz Centre for Infection Research, Baunschweig, Germany) found a link between the potential of rheumatogenic S pyogenes isolates to bind collagen, and the presence of collagen-reactive autoantibodies in the serum of patients with rheumatic fever, which might form a basis for post-streptococcal rheumatic disease.6Dinkla K Rohde M Jansen WTM Kaplan EL Chhatwal GS Talay SR Rheumatic fever-associated Streptococcus pyogenes isolates aggregate collagen.J Clin Invest. 2003; 111: 1905-1912Crossref PubMed Scopus (82) Google Scholar The protein structures of some GAS strains can be used to quickly and accurately distinguish between the general GAS and the specific GAS that can induce rheumatic heart disease and rheumatoid arthritis, but do not cause APSGN. This distinction helps to detect GAS infections that have high potential to cause rheumatic disease. Early and adequate use of antibiotics can prevent rheumatic diseases.6Dinkla K Rohde M Jansen WTM Kaplan EL Chhatwal GS Talay SR Rheumatic fever-associated Streptococcus pyogenes isolates aggregate collagen.J Clin Invest. 2003; 111: 1905-1912Crossref PubMed Scopus (82) Google Scholar The worldwide incidence of APSGN and rheumatic fever has substantially declined in recent decades. The reduction might be the result of easier and earlier access to appropriate medical care for streptococcal infections, which seems to be related to the preventive effect of overuse of antibiotics that exists globally. Antimicrobial resistance studies in GAS are important. Penicillin resistance is a serious and widespread problem worldwide, with almost all Gram-positive bacteria being resistant to penicillin. Fortunately, no naturally occurring penicillin-resistant GAS strain has been found,7Yu D Zheng Y Yang Y Is there emergence of β-lactam antibiotic-resistant Streptococcus pyogenes in China?.Infect Drug Resist. 2020; 13: 2323-2327Crossref PubMed Scopus (11) Google Scholar and GAS remains susceptible to β-lactam antibiotics. The reasons for this continued susceptibility are unknown. Globally, little attention is paid to GAS, and penicillin resistance is misunderstood in the literature.7Yu D Zheng Y Yang Y Is there emergence of β-lactam antibiotic-resistant Streptococcus pyogenes in China?.Infect Drug Resist. 2020; 13: 2323-2327Crossref PubMed Scopus (11) Google Scholar Macrolide antibiotics are recommended for patients allergic to β-lactams, but the resistance rate of GAS to macrolides and clindamycin in China is very high.8Yu D Liang Y Zheng Y Yang Y Clindamycin-resistant Streptococcus pyogenes in Chinese children.Lancet Infect Dis. 2021; 21: 1631-1632Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar Therefore, the use of such antibiotics as alternative therapies for individuals allergic to β-lactams in China could pose a risk for treatment failure.8Yu D Liang Y Zheng Y Yang Y Clindamycin-resistant Streptococcus pyogenes in Chinese children.Lancet Infect Dis. 2021; 21: 1631-1632Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar Vaccines for the prevention of GAS have been in development for decades; however, no licensed vaccine currently exists. The management of diseases caused by GAS is not uniform.9Avire NJ Whiley H Ross K A review of Streptococcus pyogenes: public health risk factors, prevention and control.Pathogens. 2021; 10: 1-17Crossref Scopus (21) Google Scholar Scarlet fever and GAS pharyngitis are both throat infections caused by GAS, but scarlet fever is listed as a communicable (or notifiable) disease and is managed as such in the UK and China, but GAS pharyngitis is not. Some countries, such as England, Wales, Japan, Canada, Norway, China, and the USA, report specific GAS diseases, but not all clinical manifestations. For example, in both Japan and the USA, only STSS is notifiable; in Canada and Norway, all iGAS diseases are notifiable; and in China, only scarlet fever is notifiable.9Avire NJ Whiley H Ross K A review of Streptococcus pyogenes: public health risk factors, prevention and control.Pathogens. 2021; 10: 1-17Crossref Scopus (21) Google Scholar In other countries, the disease is notifiable only in specific regions. In Australia, for instance, the types of GAS diseases that need to be reported vary from state to state, and in some states, GAS-related diseases do not require notification at all (appendix).10May PJ Bowen AC Carapetis JR The inequitable burden of group A streptococcal diseases in Indigenous Australians.Med J Aust. 2016; 205: 201-203Crossref PubMed Scopus (36) Google Scholar In conclusion, despite the existence of potential pandemic pathogens such as SARS-CoV-2, more attention should be paid to combined GAS or secondary GAS infections. Clinicians should avoid misdiagnosis and aim to diagnose and treat affected individuals as soon as possible. Focus should be on the possible increase of invasive GAS diseases, and clinicians should remain highly cautious and provide appropriate safety recommendations, as early identification of patients infected with iGAS and the timely initiation of specific and supportive treatment can save lives. We declare no competing interests. This research was funded by the Shenzhen Key Medical Discipline Construction Fund (SZXK032), the Guangdong Medical Research Fund (A2021437), the Hospital Level Project of Shenzhen Children's Hospital (ynkt2020-zz19), the Project of the Expert Committee on Clinical Application and Drug Resistance Evaluation of Antimicrobial Drugs of the National Health Commission (KJYWZWH-OT-02-2021-06), and the Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (SZGSP012). DY, YL, and QL contributed equally. 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